Depression is common in patients with Parkinson's Disease (PD), and is a major factor negatively impacting quality-of-life. To date, there have been no well-designed clinical trials of anti-depressant pharmacotherapy for depression in PD. Selective Serotonin Reuptake Inhibitor (SSRI) and, more recently, combined Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) anti-depressants are used as a first-line treatment for depression. However, their efficacy and tolerability in PD have not been established, and there are several important reasons why results from studies in primary psychiatric populations cannot simply be extrapolated to patients with PD. In PD, the underlying pathophysiology and somewhat atypical depressive features may result in a different anti-depressant response. Furthermore, PD patients are particularly vulnerable to antidepressant-induced extrapyramidal side effects, and a host of factors (including concomitant anti-Parkinsonian medications) may affect the general tolerability of these agents. The proposed clinical trial has been designed to compare the efficacy and tolerability of Paroxetine (an SSRI) and Venlafaxine (an SNRI) in PD patients with depression. Information regarding the effects of these medications on motor function, quality-of-life, and cognition will also be obtained. Two-hundred, twenty-eight subjects will be enrolled among 15 centers, and each subject will participate in the trial for 12 weeks. The trial will clarify many important questions regarding the treatment of depression in patients with PD. [unreadable] [unreadable]